Abstract

The intravenous administration of chlorothiazide, acetazoleamide and chlormerodrin to dogs in various combinations and in doses capable individually of producing maximal renal responses, has led to the following conclusions concerning the mechanism of action of chlorothiazide.

Chlorothiazide, by virtue of its activity as an inhibitor of carbonic anhydrase, induces natriuresis and kaluresis and causes the excretion of alkaline urine containing bicarbonate. Since these actions are qualitatively similar to those produced by acetazoleamide, and since the prior administration of acetazoleamide reduces the response to chlorothiazide, these two drugs probably act on the same renal mechanisms. However, acetazoleamide is significantly more potent than is chlorothiazide in its action as a carbonic anhydrase inhibitor.

Chlorothiazide also induces natriuresis and chloruresis in a manner analogous to that of mercurial diuretics. However, when chlorothiazide and chlormerodrin are administered in combination in doses sufficient individually to produce maximal effects, the responses are additive. We interpret these results as indicating that chlorothiazide and chlormerodrin either block different mechanisms for reabsorption of sodium and chloride ions or more probably interfere with different enzymatic reactions supplying energy to a single reabsorptive mechanism.